PROJECT SUMMARY/ABSTRACT In South Africa there are more people on treatment for HIV than ever before, placing a growing burden on health systems. While strategies for effective disease management exist for those who engage in care for HIV, the challenge of implementing best-practice at scale in the context of increasingly complex care remains. Implementation science (IS) seeks to bridge the gap between research and practice to ensure that efficacious interventions translate into effective implementation at scale. The theory of Organizational Readiness for Change (ORC) is an IS theory that posits that organizational members' shared resolve to implement a change (change commitment) and shared belief in their collective capability to do so (change efficacy) impacts successful program uptake. The Consolidated Framework for Implementation Research (CFIR), an IS framework, specifies elements in the facility inner setting that affect change commitment and efficacy. We propose to adapt scales assessing of ORC and of CFIR inner setting to the South African context to better measure the factors that should be addressed for successful translation of evidence-based interventions into clinical practice, specifically focusing on HIV, in order to close the gap towards optimized delivery of health programs in high disease burden settings. Specifically, we will use cognitive interviewing and expert consultations to culturally adapt measures of organizational readiness for implementing change (ORIC) and inner setting (CFIR) that have been developed in Western contexts (Aim 1). We will then implement the refined measures with 168 providers and 14 clinic managers in 14 South African primary care facilities in KwaZulu Natal (KZN), South Africa (Aim 2). We will assess which elements of ORC and CFIR are associated with successful implementation of a) new HIV treatment initiation and ART guidelines, and b) national decongestion programming for expedited care and medication dispensing for stable HIV patients. Results will be shared in a feedback process with experts, providers and clinic managers to validate findings. This developmental, exploratory R21 leverages an experienced research site, an established collaboration, and a multidisciplinary team of South African and US investigators to address the NIH priority of advancing research on factors associated with the successful implementation of evidence-based interventions and guidelines. This proposal can lead to targeted interventions advancing HIV program implementation and integrated care in primary care settings in high disease burden areas where scaled programming is vital.